This program is aimed at elucidating certain fundamental biochemical, biological and genetic defects which lead to mental retardation. Investigations will include a study of the mechanisms and control of the biosynthesis and degradation of glycosaminoglycans, glycosphingolipids and glycoproteins. The process of differentiation in eukaryotic cells will be studied using as a model system the in vitro conversion of limb bud mesenchyme to cartilage. Other investigations involve the study of the synthesis of glycosphingolipids in cultured cells derived from the nervous system. The enzymic basis of genetic disease resulting in mental retardation will be investigated utilizing the techniques of tissue culture and cell hybridization. Biochemical techniques will be used to isolate and determine the structure of the products stored in lysosomal diseases and enzyme assays to determine the defects in these diseases. Methods for postnatal and prenatal diagnosis of such genetic diseases will be developed.